User:Tom Gluick/glutamine synthetase/Assignment 3

Assignment and Intent
'''Assignment 3: IIB. Tertiary Structure:''' Map the two CATH domains in the GS; Include in your discussion what CATH database records ; explain the significance of each domain. In your discussion show the features of the CATH architecture and topology that provides them with the designation. As a hint you may want to use the Jena Library Jmol, which can be access through PDBsum to assist you in mapping the CATH domains. The RSCB site may not list the domains correctly.

Intent and Hope: I hoped the students would be able to illustrate the domains and structures of glutamine synthetase as defined by CATH website. I hoped the students would incorporate information found in the references into their presentation.

Student Contribution
 Glutamine Synthetase (GS) has 2 prominent CATH domains. CATH is an acronym for Class (C), Architecture (A), Topology (T), and Homologous superfamily (H), which are categories for protein classification. Each of the aforementioned levels are used to classify molecules in a hierarchical manner. The highest order classification of a molecule is Class. A molecule can be classified by any one of 4 classes: Mainly Alpha, Mainly Beta, Alpha Beta, and Few Secondary Structures. Another level of classification which is on a lower order than class is Architecture. This level of classification is used to identify the shape of the domain structure using the orientation of secondary structures but ignoring the way they are connected to each other. A third level of classification is Topology, which is also called Fold Group. This classification concerns the shared similarity of overall shape and connectivity of the secondary structures in the domain core. The Homologous superfamily refers to a fourth classification type. This hierarchy groups together protein domains which are thought to share a common ancestor, according to specific criteria.

Looking at Glutamine Synthetase in Salmonella typhimurium, we can identify 2 CATH domains, with the smaller domain encompassing residues 1-103 (in red) and the other residues 104-456 (in blue). Each of the domains are of the class Alpha Beta, however, that is the only common aspect between the two. Alpha Beta includes both alternating alpha/beta structures and alpha+beta structures. One domain begins at residue 104 and goes to residue 456. For this domain, the Architecture is a 2 layer sandwich, another example of a 2 layer sandwich can be found at http://www.cathdb.info/cathnode/3.30. A 2 layer sandwich consists of a layer of alpha helices and a layer of beta sheets forming a sandwich like structure. The Topology is Creatine Kinase; Chain A, domain 2 and the Homologous superfamily is Creatine Kinase; Chain. This domain is the larger of the two and has a COOH terminus.

The second domain in S. typhimurium begins at residue 1 and goes to residue 103. In this domain, the architecture is a roll because the alpha helices and beta sheets form a roll-like structure. The topology is ubiquitin-like, or a UB-roll due to its resemblance to a cartoon depiction of ubiquitin and the Homologous superfamily has no defined name. This domain is smaller and has an NH2 terminus. It is covalently linked to the larger COOH terminus(the first domain described in prior paragraph). This NH2 terminus is exposed compared to the buried COOH terminus of the larger domain.

For more information on CATH and the different classifications that are defined, consult the article by Orengo et al or visit the cath website at http://www.cathdb.info/

Student Contributions
Sindhu Lakkur Ejiofor Ezekwe Steven Tuyishime

Assessment
The students completed the assignment successfully. They showed the two domains in the context of the complex, showed each domain and its architecture using the SAT. The visuals were designed very well. The assignment was relatively straightforward with most information easily accessible.